Integrating
and exploring heterogeneous, multi-scale and large-scale
data produced in molecular biology

BioIntegrative Chile

BioIntegrativeChile is an Associate Team
between INRIA project-team "Dyliss" (former Symbiose
team) and the "Laboratory of Bioinformatics and
Mathematics of the Genome" hosted at CMM at
University of Chile. The Associated team is funded
from 2011 to 2013 and was renewed from 2013 to 2016.

News

November 2015: Meziane Aite joined the Dyliss team for a two-year bioanalyst contract (ADT)

October 2015: Application of shogen to bio-mining microbial community published in microbiology open

March 2015: Release of the mobyle web-server interface in chile (access to lombarde, pantograph, shogen, and bioId tools):
www access

January 2015: python encapsulations of several ASP tools (meneco, ingranalysis, caspo) are made available on github and forge.

November 2014: Ph-D defense of Sylvain Prigent.

October 2014: Marie Chevallier joined the Dyliss team
for a two-years engineer contract (ADT
ComplexBioMarkers).

We aim at combining automatic reasoning on biological
sequences and networks with probabilistic approaches
to manage, explore and integrate large sets of
heterogeneous omics data into networks of interactions
allowing to produce biomarkers of their behavior. We
shall focus on the identification of a relevant set of
biological components required to describe the
complexity of a biological phenomenon. Starting from
observations at several levels (genomics,
transcriptomics, metabolomics) we shall select with
products are relevant to the observed phenomena and
complement this list with their regulators and those
components that share the same metabolic and
signalling pathways. Our long-term goal is to exhibit
from the network obtained at the previous stage
biomarkers for the different biological phenomena
observed for an organism. Applications are mainly
focused on biomining, based on the experience acquired
at CMM in analysing several sets of data on biomining
bacteria. Methods combine a fine tuning of sequence
analysis, efficient constraint base programming and
asymptotic study of Markov models properties.

Members

Both groups are working in bioinformatics, more
precisely in integrative biology. They have developed
their own computational, statistical or mathematical
tools to integrate heterogeneous information into
networks of biological interactions, aiming to detect
relevant biological signals in complete genomes. In
Rennes, the team makes use of constraints based
approaches and discrete dynamical systems to model the
connections between several levels of cellular
observations, in order to identify key regulators from
the combination of data. In Chile, The group
develops methods of probabilistic, graph-theory and
information- theory nature to analyze omics-data
connected to industrial and academic programs of CMM,
including biomining, salmon industry and agronomical
sector. They have developed methods for biomonitoring
systems of complex metagenomics biomining samples
which was applied to detect bad-yeasts in the winery
sector. Also, they have developed methods to
reconstruct at a genomic level metabolic networks.

Evidence
characteristic biomarkers of bacteria living in extreme
environment

Our main goal for 2014-2016 will be to prove that the
bricks of integration listed above can be combined to
evidence characteristic biomarkers of bacteria living in
extreme environments: mining bacteria (A. ferrooxidans),
metal-resistant bacteria (E. faecalis), and bacteria
involved in salmon lethality (Piscirickettsia Salmonis).
This question will be addressed by coupling proba-
bilistic and static dynamical systems methods with
constraint programming. For the three targeted
applications, the chilean group strong collaborates with
biological experts who can perform experimental
validations. An important challenge will be to produce
predictions of key regulators that could be validated
with experimentations. Computationally, this means
adding criteria on experimental design to our
integration framework. The Chilean team has an expertise
in this field through the development of oligos, based
on probabilistic studies. Discretizing the criteria
appearing in their analysis in order to scale to the
size of problems raised by the integration of omics data
will be an important issue. More generally, each “brick”
of our workflow consists in solving difficult
combinatorial optimization problems. The second
challenge we will face is to propagate uncertainty
throughout the steps of the analysis, by addressing
sub-optimal problems without loosing in efficiency. This
will be done first by using the new multi-optimization
features of the most recent ASP solvers, and second by
reducing the space of admissible models by integrating
additional constraints (static analysis of biological
systems, experimental design).

Core regulators in a
reconstructed regulatory network

Lombarde. Constraints-based approach for the
identification of core regulators implied in the
response to several experimental stresses (
Preliminary results at the french Jobim conference,
long papers submitted )

Participation to patent (A. Aravena, A. Maass)
Arrangement of nucleotide sequences for the
detection and identification of transcripts
associated with the resistance or susceptibility to
infection of Salmo salar with Piscirickettsia
salmonis.

Visits

February 2011. Three weeks visit from A. Maass in
Rennes

February to July 2011. Five month visit from A.
Aravena in Rennes (co-funded by Universite Europeenne
de Bretagne and Conicyt). Methods for the construction
of transcriptional biological networks

May 2011. One month visit of Marko Budinich
(engineer) in Rennes. Reconstruction and study of
metabolic network with reduction methods.

June 2011. One month visit of Alex Di Genova
(engineer) in Rennes. Detection of structural
variations in genomes.

July 2011. Two weeks visit of Damien Eveillard
(assistant professor) in Santiago. Co-funded by
conycit. Reduction methods for the analysis of
metabolic networks.

October 2011. Two weeks visit of François Coste
(researcher) in Santiago. Co-funded by conycit.

October 2011. Two weeks visit of Jérémie Bourdon
(assistant professor) in Santiago